1. Field
The present disclosure relates to methods for predicting and monitoring efficacy of a dual-targeting agent that targets both c-Met and EGFR, methods for selecting a subject for application of the dual-targeting agent that targets both c-Met and EGFR, and methods for treating or preventing a cancer comprising administering the dual-targeting agent.
2. Description of the Related Art
A biomarker generally refers to a measured characteristic which may be used as an indicator of some change caused in an organism by an external factor. Active studies have recently been made to apply biomarkers to the diagnosis of various diseases, such as cancer, stroke, dementia, etc., and the prediction or monitoring of therapeutic effects of some agents. Among biomarkers relevant to drug development are pharmacodynamic markers (PD markers) for indicating whether drugs are functionally effective in vivo, and predictive markers for indicating the most likely response to particular drugs before administration. The use of such markers is helpful in establishing the clinical strategy of drugs. For example, a predictive marker, designed to indicate sensitivity or resistance to drug action, may be applied to the selection of patients to allow for more effective drug therapy while the action mode of a drug in individual patients can be monitored with a pharmacodynamic marker, which together can lead to the establishment of effective therapeutic strategies. Further, even in the absence of a predictive marker, a pharmacodynamic marker permits the early monitoring of responses to a drug, thus discriminating a drug-effective group from a drug-ineffective group in an early stage. Consequentially, more effective and successful drug therapies can be materialized. In addition, when applied to the monitoring of responses to a drug as a function of concentrations, a pharmacodynamic marker can be an index for calculating suitable doses of the drug.
Cancer is one of the leading causes of death. Although the development of medical techniques has brought about remarkable progress in cancer therapy, the 5-year survival rate has only improved by 10% over the past two decades. This is because cancer characteristics, such as rapid growth, metastasis, etc., make it difficult to diagnose and treat within a suitable time. The introduction of suitable biomarkers to cancer therapy would identify the characteristics of cancer to increase the opportunity of applying a suitable therapeutic in an optimal time, whereby cancer treatment could reach high success rates. For example, patients with lung cancer may differ from each other in cancer classification, genotype, and protein secretion, and thus must be treated with different, proper therapeutics. For chemotherapy using a specific drug, a corresponding biomarker, if present, would reduce the number of erroneous trials and increase the possibility of success. In this regard, it is very important to explore biomarkers for predicting or monitoring the effect of anti-cancer therapeutics. A proper biomarker, if successfully exploited, can make a great contribution to the utility and value of anti-cancer drugs and the success rate of treatment with them.
c-Met is a membrane receptor for hepatocyte growth factor (HGF) that possesses tyrosine kinase activity. HGF acts as a multi-functional cytokine which binds to the extracellular domain of c-Met to regulate cell division, cell motility, and morphogenesis in various normal and tumor cells c-Met is a proto-oncogene that takes part in a variety of mechanisms responsible for the development of cancer, such as oncogenesis, cancer metastasis, the migration and invasion of cancer cells, angiogenesis, etc., irrespectively of the ligand HGF, and thus has attracted intensive attention as a target for anti-cancer therapy. Actually, targeted therapies, such as antibodies against c-Met, have been continuously developed.
In order to increase the efficacy of therapies using c-Met-targeting drugs, it is required to develop biomarkers for predicting the effect of the c-Met-targeting drugs to select a subject who is suitable for application of the c-Met-targeting drugs, and/or for monitoring the responsiveness of a patient who has been treated with the c-Met-targeting drugs in order to establish more effective treatment strategies using the c-Met-targeting drugs.